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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | Pityriasis Lichenoides Chronica | Research

Sulfarotene, a synthetic retinoid, overcomes stemness and sorafenib resistance of hepatocellular carcinoma via suppressing SOS2-RAS pathway

Authors: Feng Qi, Wenxing Qin, Yao Zhang, Yongde Luo, Bing Niu, Quanlin An, Biwei Yang, Keqing Shi, Zhijie Yu, Junwei Chen, Xin Cao, Jinglin Xia

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Recurrent hepatocellular carcinoma (HCC) shows strong resistance to sorafenib, and the tumor-repopulating cells (TRCs) with cancer stem cell-like properties are considered a driver for its high recurrent rate and drug resistance.

Methods

Suppression of TRCs may thus be an effective therapeutic strategy for treating this fatal disease. We evaluated the pharmacology and mechanism of sulfarotene, a new type of synthetic retinoid, on the cancer stem cell-like properties of HCC TRCs, and assessed its preclinical efficacy in models of HCC patient-derived xenografts (PDXs).

Results

Sulfarotene selectively inhibited the growth of HCC TRCs in vitro and significantly deterred TRC-mediated tumor formation and lung metastasis in vivo without apparent toxicity, with an IC₅₀ superior to that of acyclic retinoid and sorafenib, to which the recurrent HCC exhibits significant resistance at advanced stage. Sulfarotene promoted the expression and activation of RARα, which down-regulated SOS2, a key signal mediator associated with RAS activation and signal transduction involved in multiple downstream pathways. Moreover, sulfarotene selectively inhibited tumorigenesis of HCC PDXs with high expression for SOS2.

Conclusions

Our study identified sulfarotene as a selective inhibitor for the TRCs of HCC, which targets a novel RARα-SOS2-RAS signal nexus, shedding light on a new, promising strategy of target therapy for advanced liver cancer.

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Title: Sulfarotene, a synthetic retinoid, overcomes stemness and sorafenib resistance of hepatocellular carcinoma via suppressing SOS2-RAS pathway
Authors: Feng Qi
Wenxing Qin
Yao Zhang
Yongde Luo
Bing Niu
Quanlin An
Biwei Yang
Keqing Shi
Zhijie Yu
Junwei Chen
Xin Cao
Jinglin Xia
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Pityriasis Lichenoides Chronica
Hepatocellular Carcinoma
Hepatocellular Carcinoma
Sorafenib
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-02085-4

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Abstract

Background

Methods

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Conclusions

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